A novel nasal co-loaded loratadine and sulpiride nanoemulsion with improved downregulation of TNF-α, TGF-β and IL-1 in rabbit models of ovalbumin-induced allergic rhinitis

Abstract

Purpose: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. Methods: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-a, TGF-b and IL-1. Results: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (À23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-a, IL-1 and TGF-b significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. Conclusion: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.

Clinical multi-omics reveals the role of Tuomin Zhiti Decoction Intervention in Allergic Rhinitis from the perspective of biological network

“…For example, IL-4, IFN-γ, and TNF-α were found to increase mucosal permeability and blocking IL-4 helped maintain the integrity of the mucosal barrier and prevented the reduction of tight junctions 24 . Cytokines such as IL-1 and TNF-αare commonly present in the body’s inflamed areas and these mediators play a key role in inflammation by recruiting additional inflammatory cells, triggering the release of more inflammatory agents, and activating afferent nerves, thereby amplifying the inflammatory response 25 . Type 2 cytokines (IL-4, IL-5, and IL-13) along with innate cytokines (IL-25, IL-33, and TSLP) were also recognized as significant biomarkers, indicating their crucial role in various allergic biological processes and allergic diseases 26 .…”

Downregulation of lncRNA CDKN2B-AS1 attenuates inflammatory response in mice with allergic rhinitis by regulating miR-98-5p/SOCS1 axis

“…The secreted cytokines (such as TNF-α, IL-5, and IFN-γ) stimulate B-lymphocyte activation and synthesize and release specific IgE, thereby sensitizing the nasal mucosa (Shinmei et al 2009 ). TNF-α, a proinflammatory factor produced by hypertrophic cells and eosinophils, is essential for the nosogenesis of AR (Iwasaki et al 2003 ; Mohamad et al 2021 ). Th2 cytokines, including IL4, IL5, and IFN-γ cells are also related to the pathogenesis of AR (Bayrak Degirmenci et al 2018 ; Zhu et al 2021 ).…”

Correlation analysis of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in refractory chronic rhinosinusitis: A retrospective study

“…22 IL-1, mainly produced by macrophages, plays an essential role in transmitting information, activating and regulating immune cells, proliferation and differentiation. 23 IL-4 is an important inflammatory index. It could activate vascular endothelial cells and inflammatory cells, and promote lymphocyte proliferation and induce adhesion molecules.…”